Cancer Immunity 3:8 (2003)

Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia

Li Li¹, Anita Schmitt², Peter Reinhardt², Jochen Greiner¹, Mark Ringhoffer¹, Bianca Vaida³, Martin Bommer¹, Markus Vollmer¹, Markus Wiesneth², Hartmut Döhner¹, and Michael Schmitt¹

¹Third Department of Internal Medicine, University of Ulm, Ulm, Germany
²Institute for Clinical Transfusion Medicine and Immunogenetics, University of Ulm, Ulm, Germany
³Department of Virology, University of Ulm, Ulm, Germany

Keywords: human, acute myeloid leukemia, dendritic cells, CD40, CD80, tumor antigens

Abstract

Acute myeloid leukemia (AML) is a clonal disease of hematopoiesis with poor clinical outcome despite recent improvements in chemotherapy and stem cell transplantation regimens. Immunotherapy with dendritic cells (DCs) eliciting specific T cell responses to leukemia-associated antigens (LAAs) might be a therapeutic option. DCs must express HLA class I/II molecules and the costimulatory molecules CD40, CD80 and CD86 to effectively activate T cells for the subsequent lysis of leukemic blasts. The expression of these antigens on DCs generated from 15 AML patients (AML-DCs) and on DCs generated from 15 healthy volunteers (HV-DCs) was analyzed by FACS. All DCs displayed the typical morphology and tested negative for B, T and NK cell markers. The sustained mRNA expression of LAAs such as PRAME, RHAMM or WT-1 proved that the AML-DCs originated from AML blasts. Compared with AML blasts, the expression of CD40, CD80, CD86 and HLA-DR was upregulated during DC culture to a median of 80-98% on AML-DCs. HLA-ABC was preserved on AML-DCs (median 95%). Expression of CD40, CD80 and CD83 remained lower on AML-DCs than on HV-DCs. AML-DCs express at least one LAA and strongly express HLA and costimulatory molecules, the prerequisites for eliciting T cell responses. AML-DCs may play a role in vaccine-based immunotherapies for AML patients.